In Silico Approach for Hepatoprotective Activity of Piper crocatum Leaf Towards CYP2E1 Protein:(TJPS-2020-0154.R2)

Abstract

Liver plays important roles in metabolism of harmful xenobiotics. Prolonged exposure to chemicals, daily dietary supplements, or pharmaceutical drugs may cause liver damage or hepatotoxicity. Acetaminophen (APAP) is a well-known pharmaceutical drug causing hepatotoxicity through generation of reactive metabolite called NAPQI (N-acetyl-p-benzoquinone imine) via Cytochrome P450 2E1 (CYP2E1) metabolism. In present study, we intended to predict the possible hepatoprotective properties of red betel (Piper crocatum) leaves. Quantitative structure activity relationship (QSAR) was used to predict the antioxidant and antiinflammatory potential of major compounds of red betel, namely eugenol, isoeugenol, chevibetol, hydroxychavicol, and allypryrocatechol. Molecular docking was performed to analyse binding mode of the compounds toward CYP2E1 protein. Network analysis using STRING was performd to deterimne pathway affected by CYP2E1. QSAR prediction shows that these compounds had moderate probability as antioxidant and antiinlammatory agents. All of the docked compounds occupied the active site of the protein. Allylpyrocatechol and Hydroxychavicol had higher calculated binding affinity than indazole known as CYP2E1 inhibitor. CYP2E1 inhibition will probably reduce liver inflammation, as it is related to many inflammatory pathway. Based on QSAR, molecular docking, and network analysis, active compounds contained in red betel leaves had hepatoprotective property through inhibition of inflammatory pathway related to CYP2E1.

;TJPS-2020-0154.R2